АSSOCIATIONS OF THE EFFECT OF LEVOTHYROXINE ON THE COURSE OF HEART FAILURE WITH POLYMORPHISMS OF B-ADRENERGIC RECEPTORS GENES
DOI:
https://doi.org/10.32782/umv-2024.2.15Keywords:
heart failure, gene, polymorphism, β-adrenoceptor, levothyroxine, disease courseAbstract
Objective: to study the associations of levothyroxine effect on the course of heart failure with polymorphisms of genes of the β-adrenoceptor system.Object and methods of the study. We included 218 patients with HF in the setting of post-infarction cardiosclerosis. Genotyping for 4 polymorphisms (Gly389Arg of the β1-adrenoceptor gene (β1-AR), Ser49Gly of the β1-AR gene, Gln27Glu of the β2-AR gene, and Ser275 of the β3-G protein subunit (GN β3) was performed by polymerase chain reaction. 109 patients (28.61%) were taking levothyroxine in individually selected doses for at least a year at the time of enrolment in the study, with euthyroid status achieved, according to indications (clinical hypothyroidism in the setting of autoimmune thyroiditis).Study results. The use of LT reduces the risk of rehospitalisation (RH) in patients with HF (OR = 0.490 (0.281–0.857), p = 0.018). There was a trend towards a reduction in the risk of achieving the combined endpoint (by 27.9%, p = 0.074). The analysis did not reveal any significant associations of the effect of LT use on the incidence of PG with polymorphisms of the β-adrenoceptor system genes. The division of patients into groups by LT dose (according to ROC analysis) revealed that the use of the drug at a dose > 0.53 μg/kg in homozygous carriers of the C allele of the Gln27Glu (c.79C>G) polymorphism of the β2-AR gene leads to a reduction in the risk of HG over two years (OR = 0.09 (0.02–0.48)). In the subgroup of patients with heterozygous (C/G) genotype, an increased risk of unfavourable HF course (increased frequency of HF, OR = 3.82 (1.29–11.31), p = 0.0087) was found in the absence of LT. No significant dependence of the effect of LT on the course of HF with other polymorphisms of the β -adrenoceptor system genes was found.Conclusions. Congenital genetic differences in the β-adrenoceptor pathway may affect the effects of levothyroxine.Thus, the use of this drug at a dose of > 0.53 μg/kg in homozygous carriers of the C allele of the Gln27Glu (c.79C>G) polymorphism of the β2-adrenoceptor gene leads to a decrease in the risk of rehospitalisation due to decompensation of heart failure within two years.
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